Elsevier

Journal of the Neurological Sciences

Volume 372, 15 January 2017, Pages 413-416
Journal of the Neurological Sciences

Microbleeds and cavernomas after radiotherapy for paediatric primary brain tumours

https://doi.org/10.1016/j.jns.2016.11.005Get rights and content

Highlights

  • Focal hemosiderin deposition (FHD), microbleeds and cavernomas, are common after brain radiotherapy for childhood primary brain tumours.

  • Young age, type of tumour, duration of the follow up and all brain radiotherapy were associated with occurrence of FHD.

  • The topographic correlation between these FHD lesions and radiation volume or area is low

  • The clinical relevance of these markers of small vessel disease is yet to be clarified.

Abstract

Background

With the expected growth and aging of the population of primary central nervous system tumours (PCNST) survivors, attention to the radiation-induced late brain injury is fundamental. Late focal hemosiderin deposition (FHD) lesions, namely microbleeds and cavernomas, are among the presumable late cerebrovascular complications associated with radiotherapy for PCNST.

Objective

To explore association between PCNST radiotherapy and the occurrence FHD lesions and to address the correlation between the topographic location of these microvascular lesions with the focal radiotherapy location.

Methods

Retrospective cohort study of 190 paediatric patients being followed for PCNST in a single referral oncological centre. The frequency of FHD lesions was compared between paediatric PCNST treated (n = 132) and not treated (n = 58) with brain radiation. Microbleed Anatomical Rating Scale (MARS) was used for systematic identification of these cerebrovascular lesions and to address the consistency between the topographic location of each lesion and the location of the focal radiotherapy area. Univariate analysis to address the role of variables such as tumour histology, location, gender and age of children at the beginning of radiotherapy, duration of follow-up and chemotherapy was performed.

Results

FHD lesions (microbleeds and cavernomas) occurred exclusively and in a high percentage (41.6%) in PCNST survivors treated with brain radiation. Younger age at the diagnosis (p = 0.031), duration of follow-up (p = 0.010) and embryonal histology (p = 0.003) positively correlated with the occurrence FHD lesions. FHD lesions were topographically concordant with the brain focal irradiation area in 3/19 (15.8%) patients from the focal RT subgroup and in 22/111 (19.8%) patients from the WBRT plus focal RT subgroup.

Conclusion

Our study, which is one of the largest to date on the topic, shows that FHD lesions are a common complication after radiotherapy for childhood PCNST. The young brain is probably more susceptible to radiation-induced late cerebrovascular injury. Diffuse small vessel disease and ceiling effect may account for the low topographic concordance we found. The clinical implications of FHD lesions in this specific population are yet to be clarified.

Introduction

The overall survival of childhood primary central nervous system tumours (PCNST) increased in the last decades [1]. As this population ages, new challenges will rise to health care providers, with emphasis on the diagnosis and management of late sequelae from treatment, including radiation-induced cerebrovascular damage [2]. Microbleeds and cavernomas can be grouped as focal hemosiderin deposition (FHD) [3] and are imaging markers of radiation-induced small vessel disease (SVD) [4]. Both are best detected using either susceptibility-weighted imaging (SWI) or T2*-weighted gradient-recalled echo (GRE) sequences [3], [5]. Microbleeds are also associated with cognitive impairment in the general population [5], [6], [7] and very recently, were found to be associated with neurocognitive dysfunction in PCNST survivors after radiotherapy (RT) [8]. The underling mechanism between RT and the occurrence of FHD is not yet fully understood. The purpose of the present study was to depict, quantify and locate FHD lesions, and to correlate its occurrence with the type, and topographic location of RT in childhood PCNST patients.

Section snippets

Study population

All paediatric patients with central nervous system tumours followed in our neuro-oncology unit from January 1973 to August 2015 were reviewed. Patients with at least 1 GRE sequence acquisition in our hospital's medical image database were included (this MRI sequence was introduced in our imaging protocol in 2006).

Data collection

All patients were regularly followed in a dedicated outpatient consultation, with at least one visit each year and at least one brain MRI each year. Data on demographic information

Results

Of the 579 paediatric patients with PCNST of our institutional database, 190 had at least one brain GRE imaging during the follow-up period. One-hundred and nine (57.3%) were male. The mean age at the diagnosis of PCNST was 8.2 years (range 0–16 years) and 7.5 years (range 0–15 years) for the RT treated (n = 132) and non-RT treated group (n = 58) respectively. The median follow-up period was 133.0 months, with 15,005.0 patient-years of follow-up. Embryonal (42.4%), ependymal (17.4%) and low grade

Discussion

In this large cohort of childhood PCNST, we have shown that FHD lesions, namely microbleeds and cavernomas, occurred exclusively in childhood PCNST patients treated with RT. In our analysis, we used the current international definitions for microbleeds and cavernomas [6], [10] and grouped them under a broader designation (FHD), which covers a spectrum of imaging changes that are closely related [4]. FHD lesions occurred in a high percentage (41.6%) of PCNST patients treated with RT. We

Authors' contribution

Conception and design: João Passos; Sofia Nunes; Hipólito Nzwalo

Acquisition of data: Sofia Nunes; João Passos; Joana Marques; Mariana Valente; António Mota

Analysis and interpretation of MRI sequences: Alexandra Borges; Ana Azevedo; Sofia Nunes; João Passos

Statistical analysis: Sofia Nunes

Article drafting: João Passos; Hipólito Nzwalo; Sofia Nunes

Article review and final approval: all authors

Disclosure

The authors have nothing to disclose.

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